The fundamental objective of this project is to determine the differentiation program of murine natural killer (NK) and killer (K) cells and to define the modulating effects of neoplasia on the production of NK and K cells. In vivo cytokinetic studies with 3H-TdR, repopulation assays and in vitro colony-forming assays are being used to determine the proliferative status and renewal rate of NK and K cells in the bone marrow and their life span in the periphery. NK-specific alloantisera, NK 1.1 and NK 2.1, and functional assays are used to probe the developmental and functional heterogeneity of NK and K cells. We are continuing to test the effect of in vivo depletion of NK and K cells during the neonatal period, using our model for specific depletion by in vivo treatment with NK\1.1 antiserum. In the future, we will test the effects of specific depletion of NK cells on: (1)\the production and maturation of NK and K cells; and (2)\the induction and growth of 3-methylcholanthrene-\and Moloney sarcoma virus-induced sarcomas. The effects of tumor growth on the production and life span of NK and K cells will also be determined.